The goal of this proposal is to develop novel reagents, approaches, and delivery systems for anti-HIV gene therapies. This is the second renewal of a proposal that began with the development of anti-Rev aptamers as potential gene therapy agents. Our initial goals have been largely reached (as will be seen in the Progress Report, C), and the nature of treatment has changed during the last several years. Therefore, this incarnation of the proposal represents a shift from earlier efforts. While we continue to develop anti-Rev aptamers as gene therapy agents, we recognize that drug resistance has become one of the chief problems confronting clinicians, and have therefore expanded our goals to include the development of multiple gene therapy agents that will simultaneously target multiple HIV proteins. Moreover, we recognize that there are numerous problems with the inauguration of gene therapy strategies for the treatment of disease, and we have therefore also begun to develop novel methods for the delivery and regulation of gene therapy agents.